The role of inhibitory neurons in the ventromedial medulla in the control of locomotion.

Mankor, J. (Joanne) (2013) The role of inhibitory neurons in the ventromedial medulla in the control of locomotion. thesis, Medicine.

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Abstract

Locomotion is a complex function that requires the control of initiation, posture, speed, rhythm, tone and direction. These features allow normal gait performances. In the elderly, gait is often impaired. This is frequently the result of a neurological disease. To develop effective treatments we need to understand the neural circuitries involved in both normal and pathological gait. To perform a motor task the integrated activity of a diverse set of neural circuits is demanded. A variety of regions in the nervous system aid in the execution of locomotion, from spinal motoneurons to spinal interneurons, to brainstem reticulospinal systems and forebrain and midbrain control regions. Motoneurons innervating different muscles are organized into distinct longitudinal columns in the ventral horn of the spinal cord. In mice, the species used in this project, the cervical cord contains motoneurons steering fore limb muscles and the lumbar cord contains motoneurons steering hind limb muscles active during locomotion. It is widely accepted that the spinal cord contains sets of interneurons that have assembled themselves into ordered networks capable of controlling activity and output of spinal motoneurons. These networks, central pattern generators (CPG’s), are the link between the brain and the motoneurons. In this project, we will focus on the projections to motoneurons from the ventromedial medulla, a part of the brainstem. These projections descend trough the reticulospinal system. Besides excitatory and serotonergic neurons, the medulla contains inhibitory reticulospinal (vgat+) neuronen, projecting to motoneurons. Interestingly, some motoneuron groups do receive a larger projection from this system than others and this system seems to project directly to motoneurons, bypassing the CPG’s. We would like to know which motoneuron pools the most projections receive and what the function of this inhibitory system is. New techniques allow us to genetically dissect the role of inhibitory, excitatory and serotonergic neurons in the medulla. The use of conditional adeno associated viral vectors (AAVs) makes it possible to visualize only those neurons that express cre-recombinase with a tracer. An antergrade tracer is injected in vgat+ neurons in the ventromedial medulla and is transported to the ventral horn of the spinal cord, A retrograde tracer is injected in the muscles and is transported to the motoneurons in the ventral horn of the spinal cord. Immunohistochemistry allowed the visualization of both tracers in the confocal microscope. We expected the inhibitory projections from the VMM to target specific areas of the spinal ventral horn and not being evenly distributed to every motoneuron pool. The results do show a difference between the amount of projections received by motoneuron pools of different muscles. In the cervical enlargement, the triceps does get a hard hit of this inhibitory medullary system and in the lumbar enlargement, the gastrocnemius is striking. Looking at the total numbers, the lumbar enlargement seems to get a slightly stronger projection than the cervical enlargement. However, the relatively small amount of data per muscle and per mouse did not allow the performance of meaningful statistical tests. In the future, implanting the triceps and the gastrocnemius muscles with EMG wires is likely to produce interesting data.

Item Type:	Thesis (Thesis)
Supervisor name:	Boddeke, prof. dr. H.W.G.M.
Supervisor name:	VanderHorst, Veronique and Dept. of Neurology and Beth Israel Deaconess Medical Center and Boston
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:52
Last Modified:	25 Jun 2020 10:52
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/1309

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